Polyarteritis Nodosa - PAN

Diagnosis

Indications for Testing

Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)

Laboratory Testing

• Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
  • CBC – rule out infection
  • Urinalysis (UA) – hematuria, proteinuria, red blood cell casts
  • C-reactive protein (CRP) – frequently elevated
    • Preferred test to detect inflammatory processes (Choosing Wisely: 20 Things Physicians and Patients Should Question, American Society for Clinical Pathology, 2017)
    • If CRP not available, order erythrocyte sedimentation rate (ESR)
• Testing to consider to rule out other diagnoses
  • Antineutrophil cystoplasmic antibodies (ANCA) – rarely positive, rule out ANCA-associated vasculitis
  • Hepatitis B surface antigen – rule out concomitant chronic hepatitis
  • Antinuclear antibodies (ANA) – rule out connective tissue diseases
  • Antiglomerular basement membrane antibodies – rule out an antiglomerular basement membrane disease (anti-GBM)

Histology

• Small- and medium-size artery necrotizing vasculitis with absence of glomerulonephritis
• Arterioles, capillaries, and/or venules – most affected
• Immunofluorescence fails to demonstrate complement or immunoglobulin in vessel walls

Imaging Studies

Angiography – microaneurysms and stenoses of medium vessels.

Differential Diagnosis

• Alport syndrome
• Connective tissue diseases
  • Systemic lupus erythematosus
  • Mixed connective tissue disease
  • Systemic sclerosis (scleroderma)
• Anti-GBM disease (Goodpasture syndrome)
• Vasculitis – microscopic polyangiitis
• Infection
  • Mycobacterium tuberculosis
  • Endocarditis
  • Hepatitis B/hepatitis C
  • Treponema pallidum 
  • Cytomegalovirus
  • Epstein-Barr virus
  • HIV
  • Plasmodium spp
• Cryoglobulinemia
• Malignancy
  • Lymphoma
  • Plasma cell dyscrasias

Background

Epidemiology

• Incidence –16-25/million for systemic vasculitis as a group (includes eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, and granulomatosis with polyangiitis)
• Age – peak onset in 50s
• Sex – M:F, equal

Risk Factors

Chronic hepatitis B

Clinical Presentation

• Constitutional – fever, malaise, weight loss, arthralgias
• Cardiovascular – acute coronary syndrome
• Dermatological – vascular purpura, livedo reticularis, lower extremity ulcers, subcutaneous ulcers
• Gastrointestinal – nonspecific abdominal pain, gastrointestinal bleeding, bowel perforation
• Neurological – mononeuropathy multiplex
• Renal – renovascular hypertension, vascular nephropathy

Pediatrics

Epidemiology

• Age – peak is 9-11 years
• Sex – M<F, slight

Clinical Presentation

• Tends to be a more limited disorder than in adults
• Constitutional – fever, malaise, weight loss
• Musculoskeletal – arthritis/arthralgia, myositis, myalgia
• Renal – vascular hypertension, hematuria, proteinuria
• Neurological – peripheral neuropathy
• Gastrointestinal – nonspecific abdominal pain
• Dermatological – livedo reticularis, skin nodules, skin infections

Indications for Testing

Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)

Laboratory Testing

• Nonspecific testing
  • CBC – anemia, leukocytosis, thrombocytoses
  • C-reactive protein (CRP) – usually elevated
    • Preferred test to detect inflammatory processes  (Choosing Wisely: 20 Things Physicians and Patients Should Question, American Society for Clinical Pathology, 2017)
    • If CRP not available, order erythrocyte sedimentation rate (ESR)
  • Urinalysis (UA) – proteinuria, hematuria, red cell casts
  • Electrolytes – increases in blood urea nitrogen (BUN)/creatinine not uncommon
• Antineutrophil cystoplastic antibodies (ANCA) – rarely positive

Differential Diagnosis

• Infection
  • Mycobacterium tuberculosis
  • Endocarditis
  • Hepatitis B/hepatitis C
  • Treponema pallidum
  • Cytomegalovirus
  • Epstein-Barr virus
  • HIV
  • Plasmodium spp
• Vasculitis
  • Microscopic polyangiitis
  • Kawasaki disease
  • IgA vasculitis
• Connective tissue diseases
  • Systemic lupus erythematosus
  • Mixed connective tissue disease
  • Systemic sclerosis – scleroderma
• Alport syndrome